Adverse Drug Reactions in Patients Receiving Systemic Antifungal Therapy at a High‐Complexity Hospital

Abstract

The aim of the present study was to determine the frequency of adverse drug reactions (ADRs) associated with the use of systemic antifungal drugs in patients hospitalized at a high-complexity hospital. In addition, factors associated with ADRs were investigated. This cross-sectional retrospective study involved the investigation of 183 medical records of patients receiving systemic antifungal therapy. Antifungal drugs were classified using the fourth level of the Anatomical Therapeutic Chemical System. ADR causality was classified using the Naranjo algorithm. Drug interactions were assessed using DRUG-REAX software. Data were analyzed with descriptive statistics and univariate and multivariate logistic regression. A total of 53 patients (29.0%) had at least 1 ADR involving antifungals. Ninety-six ADRs were detected. The main ADRs observed were an infusion reaction in 24 patients (25.0%), hypokalemia in 22 (22.9%), nephrotoxicity in 18 (18.7%), and hepatotoxicity in 15 (15.6%). Amphotericin B and voriconazole were associated with ADRs of major clinical impact. Eleven of the ADRs (11.4%) were related to drug interactions. The following 3 factors were contributors to the multivariate model for the occurrence of ADRs caused by antifungal drug use: neoplasm diagnosis (odds ratio [OR], 3.9; 1.9-7.9), length of hospital stay (OR, 2.2; 1.1-4.5), and the use of ≥13 drugs (OR, 3.4; 1.6-7.2). Our study revealed positive associations between the occurrence of ADRs and diagnosis of a neoplasm, the length of stay, and the use of multiple drugs concomitant with antifungals. These risk factors should be considered in antifungal stewardship, among other actions, to promote the rational use of antifungal agents.

Autoinhibitory properties of the parent but not of the N‐oxide metabolite contribute to infusion rate‐dependent voriconazole pharmacokinetics

“…These concentrations still were safe and only had marginally more (70 vs. 60) treatment‐related adverse events. Overall, voriconazole is well tolerated compared to other azole antimycotics and infusion reactions are rare .…”

Antifungal Peptides as Therapeutic Agents

“…The low diversity of mechanisms of action of current treatments represents a problematic situation when fungal pathogens are multi-resistant to antifungals (Rautenbach et al, 2016). Furthermore, existing antifungal drugs are associated with adverse drug reactions such as hypokalemia, infusion reaction, nephrotoxicity, hepatotoxicity and gastrointestinal affections, among others (Chen et al, 2011;de Souza et al, 2016;Kyriakidis et al, 2017;Pappas et al, 2018). Some antifungal drugs affect common eukaryotic targets present both in pathogenic fungi and human cells (Rautenbach et al, 2016).…”

The impact of pharmacist‐led antifungal stewardship interventions in the hospital setting: a systematic review

“…Mortality rates for IFDs are in excess of 30–50% 1–3 . The use of antifungal agents as prophylaxis and for treatment of IFD are associated with a substantial economic burden, 4 high rates of adverse drug reactions, 5 significant drug–drug interactions 6 and rising resistance to existing antifungals 7,8 . Observational studies have described high rates of suboptimal antifungal prescribing in the hospital setting 9–14 .…”